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991.
Precision of molecular time estimates 总被引:24,自引:0,他引:24
992.
Epidermal growth factor activates m-calpain (calpain II), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation
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Glading A Bodnar RJ Reynolds IJ Shiraha H Satish L Potter DA Blair HC Wells A 《Molecular and cellular biology》2004,24(6):2499-2512
How m-calpain is activated in cells has challenged investigators because in vitro activation requires near-millimolar calcium. Previously, we demonstrated that m-calpain activation by growth factors requires extracellular signal-regulated kinase (ERK); this enables tail deadhesion and allows productive motility. We now show that ERK directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (EGF)-induced calpain activation in vitro and in vivo. Replacing the serine with alanine limits activation by EGF and subsequent cell deadhesion and motility. A construct with the serine converted to glutamic acid displays constitutive activity in vivo; expression of an estrogen receptor fusion construct produces a tamoxifen-sensitive enzyme. Interestingly, EGF-induced m-calpain activation occurs in the absence of increased intracellular calcium levels; EGF triggers calpain even in the presence of intracellular calcium chelators and in calcium-free media. These data provide evidence that m-calpain can be activated through the ERK cascade via direct phosphorylation and that this activation may occur in the absence of cytosolic calcium fluxes. 相似文献
993.
994.
Anthony NG Fox KR Johnston BF Khalaf AI Mackay SP McGroarty IS Parkinson JA Skellern GG Suckling CJ Waigh RD 《Bioorganic & medicinal chemistry letters》2004,14(5):1353-1356
Footprinting, capillary electrophoresis, molecular modelling and NMR studies have been used to examine the binding of a short polyamide to DNA. This molecule, which contains an isopropyl-substituted thiazole in place of one of the N-methylpyrroles, is selective for the sequence 5'-ACTAGT-3' to which it binds with high affinity. Two molecules bind side-by-side in the minor groove, but their binding is staggered so that the molecule reads six base pairs, unlike the related natural products, which tend to bind to four-base-pair sequences. The result suggests that high affinity and selectivity may be gained without resort to very large molecules, which may be difficult to deliver to the site of action. 相似文献
995.
Schwartz CE May MM Carpenter NJ Rogers RC Martin J Bialer MG Ward J Sanabria J Marsa S Lewis JA Echeverri R Lubs HA Voeller K Simensen RJ Stevenson RE 《American journal of human genetics》2005,77(1):41-53
Allan-Herndon-Dudley syndrome was among the first of the X-linked mental retardation syndromes to be described (in 1944) and among the first to be regionally mapped on the X chromosome (in 1990). Six large families with the syndrome have been identified, and linkage studies have placed the gene locus in Xq13.2. Mutations in the monocarboxylate transporter 8 gene (MCT8) have been found in each of the six families. One essential function of the protein encoded by this gene appears to be the transport of triiodothyronine into neurons. Abnormal transporter function is reflected in elevated free triiodothyronine and lowered free thyroxine levels in the blood. Infancy and childhood in the Allan-Herndon-Dudley syndrome are marked by hypotonia, weakness, reduced muscle mass, and delay of developmental milestones. Facial manifestations are not distinctive, but the face tends to be elongated with bifrontal narrowing, and the ears are often simply formed or cupped. Some patients have myopathic facies. Generalized weakness is manifested by excessive drooling, forward positioning of the head and neck, failure to ambulate independently, or ataxia in those who do ambulate. Speech is dysarthric or absent altogether. Hypotonia gives way in adult life to spasticity. The hands exhibit dystonic and athetoid posturing and fisting. Cognitive development is severely impaired. No major malformations occur, intrauterine growth is not impaired, and head circumference and genital development are usually normal. Behavior tends to be passive, with little evidence of aggressive or disruptive behavior. Although clinical signs of thyroid dysfunction are usually absent in affected males, the disturbances in blood levels of thyroid hormones suggest the possibility of systematic detection through screening of high-risk populations. 相似文献
996.
997.
High density lipoprotein prevents oxidized low density lipoprotein-induced inhibition of endothelial nitric-oxide synthase localization and activation in caveolae 总被引:15,自引:0,他引:15
Uittenbogaard A Shaul PW Yuhanna IS Blair A Smart EJ 《The Journal of biological chemistry》2000,275(15):11278-11283
Oxidized LDL (oxLDL) depletes caveolae of cholesterol, resulting in the displacement of endothelial nitric-oxide synthase (eNOS) from caveolae and impaired eNOS activation. In the present study, we determined if the class B scavenger receptors, CD36 and SR-BI, are involved in regulating nitric-oxide synthase localization and function. We demonstrate that CD36 and SR-BI are expressed in endothelial cells, co-fractionate with caveolae, and co-immunoprecipitate with caveolin-1. Co-incubation of cells with 10 microgram/ml high density lipoprotein (HDL) prevented oxLDL-induced translocation of eNOS from caveolae and restored acetylcholine-induced nitric-oxide synthase stimulation. Acetylcholine caused eNOS activation in cells incubated with 10 microgram/ml oxLDL (10-15 thiobarbituric acid-reactive substances) and blocking antibodies to CD36, whereas cells treated with only oxLDL were unresponsive. Furthermore, CD36-blocking antibodies prevented oxLDL-induced redistribution of eNOS. SR-BI-blocking antibodies were used to demonstrate that the effects of HDL are mediate by SR-BI. HDL binding to SR-BI maintained the concentration of caveola-associated cholesterol by promoting the uptake of cholesterol esters, thereby preventing oxLDL-induced depletion of caveola cholesterol. We conclude that CD36 mediates the effects of oxLDL on caveola composition and eNOS activation. Furthermore, HDL prevents oxLDL from decreasing the capacity for eNOS activation by preserving the cholesterol concentration in caveolae and, thereby maintaining the subcellular location of eNOS. 相似文献
998.
Phorbol 12-myristate 13-acetate induces protein kinase ceta-specific proliferative response in astrocytic tumor cells 总被引:1,自引:0,他引:1
Hussaini IM Karns LR Vinton G Carpenter JE Redpath GT Sando JJ VandenBerg SR 《The Journal of biological chemistry》2000,275(29):22348-22354
Protein kinase C (PKC) activation has been implicated in cellular proliferation in neoplastic astrocytes. The roles for specific PKC isozymes in regulating this glial response, however, are not well understood. The aim of this study was to characterize the expression of PKC isozymes and the role of PKC-eta expression in regulating cellular proliferation in two well characterized astrocytic tumor cell lines (U-1242 MG and U-251 MG) with different properties of growth in cell culture. Both cell lines expressed an array of conventional (alpha, betaI, betaII, and gamma) and novel (theta and epsilon) PKC isozymes that can be activated by phorbol myristate acetate (PMA). Another novel PKC isozyme, PKC-eta, was only expressed by U-251 MG cells. In contrast, PKC-delta was readily detected in U-1242 MG cells but was present only at low levels in U-251 MG cells. PMA (100 nm) treatment for 24 h increased cell proliferation by over 2-fold in the U-251 MG cells, whereas it decreased the mitogenic response in the U-1242 MG cells by over 90%. When PKC-eta was stably transfected into U-1242 MG cells, PMA increased cell proliferation by 2.2-fold, similar to the response of U-251 MG cells. The cell proliferation induced by PMA in both the U-251 MG and U-1242-PKC-eta cells was blocked by the PKC inhibitor bisindolylmaleimide (0.5 micrometer) and the MEK inhibitor, PD 98059 (50 micrometer). Transient transfection of wild type U-251 with PKC-eta antisense oligonucleotide (1 micrometer) also blocked the PMA-induced increase in [(3)H]thymidine incorporation. The data demonstrate that two glioblastoma lines, with functionally distinct proliferative responses to PMA, express different novel PKC isozymes and that the differential expression of PKC-eta plays a determining role in the different proliferative capacity. 相似文献
999.
Exposure of carcinoma cell lines to the antibiotic geldanamycin induces the degradation of ErbB-2, a co-receptor tyrosine kinase that is frequently overexpressed in certain tumors. Using ErbB-2 mutants expressed as chimeric receptors or green fluorescent protein fusion proteins, we report that the kinase domain of ErbB-2 is essential for geldanamycin-induced degradation. The kinase domain of the related epidermal growth factor receptor was not sensitive to this drug. The data further indicate mechanistic aspects of ErbB-2 degradation by geldanamycin. The data show that exposure to the drug induces at least one cleavage within the cytoplasmic domain of ErbB-2 producing a 135-kDa fragment and a 23-kDa fragment. The latter represents the carboxyl-terminal domain of ErbB-2, whereas the former represents the ectodomain and part of the cytoplasmic domain. Degradation of the carboxyl-terminal fragment is prevented by proteasome inhibitors, whereas degradation of the membrane-anchored 135-kDa ErbB-2 fragment is blocked by inhibitors of the endocytosis-dependent degradation pathway. Confocal microscopy studies confirm a geldanamycin-induced localization of ErbB-2 on intracellular vesicles. 相似文献
1000.
Cheroske AG Williams SL Carpenter RC 《Journal of experimental marine biology and ecology》2000,248(1):1-34
Disturbance in coral reef environments commonly results in an algal community dominated by highly productive, small filamentous forms and cyanobacteria, collectively known as algal turf. Research on the types of disturbance responsible for this community structure has concentrated mainly on biological disturbance in the form of grazing, although physical and other forms of biological disturbances may be important in many coral reef areas. On the reef flat in Kaneohe Bay, Oahu, Hawaii, algal turfs grow primarily upon coral rubble that tumbles with passing swells. We manipulated the frequency of rubble tumbling in field experiments to mimic the effects of physical disturbance by abrasion and light reduction on algal biomass, canopy height, and community structure. Treatments approximated a gradient of disturbance intensities and durations that occur on the reef flat. Although sea urchins and herbivorous fishes are not widespread and abundant on the reef flat, biological disturbances to algal turf communities in the form of herbivory by small crabs and abrasion by tough macroalgae contributed significantly to the variation in algal turf biomass. Within all experiments increasing disturbance significantly reduced algal biomass and canopy heights and the community structure shifted to more disturbance-tolerant algal forms. This study shows that the chronic physical disturbances from water motion and biological disturbances other than grazing from large herbivores can control algal communities in coral reef environments. 相似文献